exam 2: lecture 1

Question 1

what was the earliest diuretic used in medicine then what came after up until 1920s?

what medicine was first DESCRIBED as a durietic?

Answer 1

caffeine

mercury came up until 1920

first describe: dijoxin from fox glove plant

Question 2

what was the first dureritc made and what year? what is the story behind it and who was the work based off of?

Answer 2

acetazolamide in 1937

the story is that people thought penacillim was #1 ABX but the #1 ABX was sulfa based / sulfaoamide ABX made in the NAZI germany —— acetazolmibe is a derivative of that which came in 1937!

based on GARICK PARDOLLA (who is not a nazi)

Question 3

what is the order of the diuretics made?

Answer 3

1937 - acetozolamide

next = thaizide duiretics

1960 furosemide loop (s/e of thiazide and loop were it casues hypokalemia)

K sparing durietics v

2010 = SGL2i

Question 4

what are the four loop diueretics and its half life/bioavility descritpion?

Answer 4

FBTE
1. furosemide (lasix) = bioavbianiltiy pt dependnat, 6 hour half life, sulfa based

2. bumetanide (bumex) = better bioaviabailty, short half life than laxis, sulfa based
3. torsemide (demedex) = better bio than laxis, half life is LONGER than laxis, sulfa based
4. ethacynic acid = given to those w sulfa allerhgy

Question 5

what is the SOA and MOA for loop direutics?

Answer 5

SOA - ascending loop of henle

MOA:
1. inhibits Na/K transporter in lumen side
2. Na K Cl build up inside lumen
3. water follow = causing duiresis (ode urine)

Question 6

whats a good benefit to loop durietics regarding kidney?

Answer 6

it increases COX which increases prostaglandin which increases renal blood flow and maintanes GFR

Question 7

what ions are lost and HOW? explain how Mg and Ca are lost?

Answer 7

lost ions: NA K CL, Mg, Ca, H

MG and Ca are lost bc normally K is in a cycling betwene lumen and basolateral side and this helps Mg and Ca gets absorbed. but when you give someone loop duiretic, you inhibit this K cylcing –> NET POSTIVE CHARGE of +10mV outside which REPELLS Mg/Ca –> causes Mg/Ca to go into the lumen = LOST

Question 8

how is K lost with loop durietics?

Answer 8

when you inhibit Na/Cl transportioer you have ode Na and Cl in the lumen, in the distal tubule, you see there is ode Na Cl so what the tubule does is there is passive reabsoprtion of NA and K is excreted out more into the lumen to balance it out

Question 9

what is the ions gain with loop duritiecs and what is post diuretic NACL retention?

Answer 9

ions gain = uric acid –> gout

post duiretic NaCl retention is when the med wear off, your kidney compensate the salt lost so make sure ur pt is on a low Na diet to counter act this

Question 10

what are the indication for loop dureitics?

Answer 10

when do you give loop durietics?
1. acute pulmonary edema - reduce preload, causing naturesis
2. edamtous conditions
3. acute hypercalcemia
4. renal failure - to maintain GFR, maintain good blood flow
5. HF - dont give it alone though relax my guy

Question 11

what are the untoward effect for loop durietics?

Answer 11

1. **hypoK **- this is why its bettter to give someoen loop durietics + K+ sparing drug
2. hypocholeremic alkalosis - loss Cl and loss of H
3. HypoMg - leading to arrthymias and musucle probelms
4. **HypoCa **- compenstatory in parathyroid homrone and Vit D activity so make sure you check peri-post menopausal women Ca levels
5. **Hyperuricemia **
6. **metobolic issues **- increases LDL and tri
7. ototoxicity - titintis or fullness in ear or deaf
   - drug can affect BF to strai vascularis, BF to endo and perilymph, or deposit in the ear inside
8. dueiritc failure can happen - someone on it for too long, the loss of blood and trigger renin release triginger ANG2, triggering SGL2 transporter –> Na and glucose will be reaborbed to balance out loopD

Question 12

what are the three SGLT2i drugs?

Answer 12

Canaglifozin (infacana)
Dapagliflozin (farxida)
Empaglifozin (gardiance)

*they were devleop to tx T2DM by removing glucose without causing hypoglycemia

Question 13

what is the MOA for SGLT2i? whats a benfit of SGLT2i?

Answer 13

MOA is proximal tubule

normally, Na rushes DOWN its conc gradient and takes glucose with it == this is show glucose and Na is reabsorbed

it ALSO inhibits the Na/K transporter which is found in the kidney and cardiac myocytes
- when this gets fucked up it sequesters Calcium which is bad for heart and kidney so by inhibtiing this, it stops the negative effects!!

SGLT2i also inhibits symapthetic outflow so stops the release of noepi+epi

Benefit: it triggers erythropoesis!! it increases HIF and triggers erythropoesis, increases heamtocrit and O2 delivery to heart :)

Question 14

what are the indication for SGLT2i?

Answer 14

give someone SGLT2i to:

1. HF once they become sx
2. DM2
3. chornic kidney diease (with or w/o DM)

imrpoves M&M regardless!

Question 15

what is the untoward effects of SGLT2i?

Answer 15

1. UTI - buildiup of glucose in the urine
2. **mycotic infection of perinium **= FAMOUS!
3. bone fractures in those peri-post menopasul women = inhibits parathyroid hormone and VID homeostasis

Question 16

what are the two drugs for thaizide? which is more potent?

Answer 16

1. hydrocholorthiazide
2. chlorthalidone - MORE POTENT

Question 17

what is the SOA and MOA for thaizide?

Answer 17

SOA = DCT
MOA=
1. thaizides will enter the epithelial cells from lumen through OAT 1 and OAT 3 receptors.
2. this will inhibit Na/Cl pump and Na and Cl will stay in the lumen
3. water will follow = diuertic effect

Question 18

why is Ca lost in thaizide rx?

Answer 18

so normally, thaizide will bind to OAT1 and OAT 3 and inhibit the Na/Cl trasnproted so NA and Cl will build up in the lumen of the DCT

becasue there is alot of Na in the DCT, the NaCl exchanger will be activated and Na will enter the cell through this and Ca will be reabsored

Question 19

how is uric acid gained with thaizide medications?

Answer 19

1. thiazides enter the cell throuhg OAT 1 and 3.
2. it takes thaizide form blood to the lumen via OAT
3. thaizide COMPETES with uric acid and so uric acid cannot be filtered OUT FROM the blood then

NET EFFECT: thaizide stops the excretion of uric acid from blood to urine (stays in the blood)
and - it enahnces reabsorption of UA from lumen into blood

Question 20

why is thaizide better in black pt?

Answer 20

better in blacks becasue black people have higher CK levels and CK is good bc it regenerates ATP so Na/K ATPase can function

Question 21

what ions are gained and lost with thaizide?

Answer 21

gain: Ca, uric acid
lost; Na, Cl, K

Question 22

whats a benefit of taking thaizide regarding the kidney?

Answer 22

increases COX, increases prostaglandin, increases vasodilation, GFR, blood flow

Question 23

what is the indication and S/E for thaizide?

Answer 23

indication:
1. HTN in black pt: intial therapy
2. Nephrolithaisis : since Ca is gained, only if stones form
3. MILD edema
4. diabetics insipidus

S/E
1. best tolerated drug for HTN :)
2. NO OTOTXOCIITY HERE UNLIKE LOOP DUREITICS
3. glucose intolerance –> hyperglycemia
4. hyperuricemia/gout = unique!

Question 24

what are the four K sparing diuretics? SOA?

Answer 24

SEAT
1. spironolactone - aldosterone analog, inhibits the aldosterone receptor
2. eplerenone - spiro analog, more specificity for aldo receptor, LESS S/E
3. amiloride - works in DCT to inhibit NA channal, prevent efflux of K
4. Triamtrene = works in DCT to inhibit NA channal to prevent efflux of K

SOA: DCT and CD

Question 25

what is the MOA of K+ sparing drugs? what ions are gained + lost?

Answer 25

MOA: SEAT
*(normally, aldosterone brings in Na and water and excretes K/H) *
1. Spiro and eplerenone
- Rx inhibit the aldoesterone receptor to PREVENT reabsorption of Na and water –> causes prevention of excretion of K and H (K sparing)

2. amiloride and traimterene
   - these inhibit NA channel in the DCT/CD –> prevents PASSIVE reabsorption of the Na in exchange for K

ions gian: K
ions lost: Na Cl

Question 26

what are the indication and S/E for K+ sparring drugs

Answer 26

indications: DONT GIVE DRUG ALONE!!
1. edema (given w loop diuretic)
2. HTN (given w thaizide)
3. HF (give spiro and eplerenone) (given w loop, acei, or BB)
4. **post MI ** “E is for eplerenone” - improved mortality, if they have post MI w reduced EJ, give eplerenone
5. Hyperaldoesteronism
- primary: conns syndrome with aldosterone secreting tumor
- secondary: use SPIRO
- in live failure, ascites can happen and so high volume, increases renin, increases aldostrone
- aldoesterone is also metabolized in liver so liver failure can prevent this
- aldesotrone travels in blood w albumin in liver fialure no albumin so more free form drugs

S/E
1. hyperkalemia
2. gynecomastia
3. kidney stone = SMALL FRACTION OF PT

Question 27

what are the 4 carbonic anhydrase inhibitors?

Answer 27

AMDB
1. acetazolamide - prevents Na bicarbonate reabsroption
2. Methazolamide - used in gluacoma
3. dorzolamide + brinzolamide = targets only ciliary body in eye used for glaucoma too

Question 28

whats the SOA/MOA for carbonic anhydrase?

Answer 28

SOA (AMDB) = proximal tubule for A + M
only cilliary body for D + B

MOA:
1. there is a Na/H transport that will bring Na into the cell and H into the lumen
2. H will bind with bicarbonate to make carbonic acid
3. in the lumen, carbonic anhydrase will break carbonic acid into H2O and CO2
4. H2O and CO2 will go INTO THE CELL and by the same enzyme be broken into bicarbonate and H
5. bicarbonate will be reabsorbed back in blood and H will go back to the lumen for cycle to repeat

WITH CARBONIC ANHYDRASE INHIBITOR:
1. acetazolimide PREVENTS reabsorption of Na-bicaronate in the lumen so bicarbonate builds up, water follows, = diuresis

Question 29

what ions are lost for carbonic anhydrase inhibators?

Answer 29

lost: na-bicarbonate

Question 30

what are the indication for carbonic anhydrase inhibators and what is the untoward effects?

Answer 30

Indication:
1. nephrolithiasis - some stones form in acidic urine like urate or cystine stones
2. **metabolic alkalosis: **
3. acute mountain skiness - aceta induces metabolic acidosis
4. gluacoma - D + B = you prevent carbonic anyhdrase from making AH whcih is helpful

S/E
1. metabolic acidosis
2. renal stone (phosphaturia or hypercalciuria)
3. hypoK
4. thombocytopenia, aplastic anemia =rare
5. hyperammonemia = CONTRAINDICATED IN ADVANCE LIVER DIEASE. WHY?
- normally, ammona goes in the urine + H to make ammonium which cant be reabsorbed so its excreted. this requires acidic urine. however, if urine is alkaline, thers no H to make ammonium so ammonia is reabsorbed
- BIG TISSUE FOR THOSE W LIVER FAILURE BC IT CAN LEAD TO HYPERAMMONEMIA

Question 31

what is mannitol and the SOA, MOA, indicatiojn?

Answer 31

mannitol = synthetic drug filtered in glomerulus, NOT reabsorbed and casues osmosis!!!

SOA: anywhere where its permable to water like PT, LOH, CD

MOA: mannitol cannot be broken down, it has dueiretic effect by osmosis

indication:
1.** acute glacoma **- decreases IOP, takes fluid out
2. cerebral edema - decreases brain swelling casues by trauma or surgery

Question 32

who is david kushman, surgeo farrera, john vain?

Answer 32

surgeo farrera in 1965 was the first to look at brazil viper venom and found that it inhibits ACE in rats it died by hypotension

john vain gave it to dogs same thing

david kushman gave it to human and it good- captopril = first ACEi

Question 33

what are the ACEi drugs? CEL-RB

Answer 33

untoward effect: HTN, altered sense of taste (Dysgeusia )
1. Captopril - FIRST IN CLASS 1978 - had issues, 2 hour half life
2. Enalapril - pro drug, delayed onset, last 12-24 hours, LESS HTN, less Dysgeusia
- PT W HF w enalapril = reduction in M/M
3. Lisinopril = last 24 hours!!! unmetabolized by kidney
4. Ramipril = better bioava, longer acting, less Dysgeusia
5. benazepril = long acting

Question 34

what is the MOA of ACEi?

Answer 34

1. ACEi inhibits angiotension converting enzyme so it stops the production of ANG2
2. bradykinin increases
   Good - upregualte COX, increases prostaglandin, vasodilatiojn good perfusion
   BAD - angiodema, DRY cough swelling
3. ACEi goes to endo cell and stops ROS so NO increases which casues vasodialtion and decreases BP

Question 35

what is the indication and S/E for ACEi?

Answer 35

indication:
1. chronic kidney disease = pt with DM who get microalbuminuria should be given ACEi
2. HTN - stops ANG2 , stop vasoconstirction, stops ROS, doe vasodialtion
3. HF - M/M reduced w ACEi
4. post MI w reduced EF - helps stop remodeling
5. angina = given along BB

S/E:
- hypotension = NO increases
- HyperK = stops aldoesterone which secretes K
- Dry cough
- angioedema
- DONT USE FOR ACUTE RENAL FAILURE = AA is ANG2 dependent if you lose ang2 then poor GFR
- obv dont use in pregnancy

Question 36

what is ARB? what are the 7 drugs for ARBS?

Answer 36

losartan - FIRST DRUG 1995
valsartan
candesartan
irebesartan
eprosartan
telmisartan
olmesaratan

ARB was introduced bc with soemoen with ACEi, there are other enyzme tht culd produce ARG 2, or body will make more renin and ANG1, and due to high lelves of bradykinin

Question 37

what is the MOA, indication, untoward effect of ARB?

Answer 37

MOA: blocks ANG2 receptor, reduces ROS made in endo cell, better NO, more vaosdilation

indication: same as ACEi (chronic kidney disease, HTN, post MI, HF, angina)

S/E: similair to ACEi but without cough!!! dont give to pregnant pt

Question 38

what is sacubitril + valsaran? what is aliskiren?

Answer 38

sacubitril + valsartan = ENTRESTO
- sacubitrial inhibits nepristyl enzyme (which breaks down BNP and ANP – secreted by heart and kidney in response to stretch)

–> rec to give pt w HF w reduced or perserved EF ENTRESTO

Aliskiren = inhibits renin (renin turns angiotension to ANG1)

- contraindicated in DM bc it casues stroke and CV events, kideny failure and hyperkalemia 

- dont mix this w ACEi  or ARB